Recruitment of patients was initiated at Connecticut Children's Medical Center in Hartford, CT and at the Hospital for Sick Children in Toronto. To date, 28 patients with inflammatory bowel disease have been recruited. We are on target to reach our goal of recruitment for Crohn's disease and ulcerative colitis patients. We are now focusing our recruitment efforts on normal controls and "inflammatory" (rheumatologic) controls. Our preliminary results of bone density indicate that approximately 50% of children with Crohn's disease have osteopenia at least in one site (lumbar spine, hip, total body) at the time of diagnosis. In addition, patients recruited in Toronto are also undergoing radiological bone density measurements with heel ultrasonography. So far, there is a 100% correlation between DEXA and ultrasonographic determination of osteopenia. These observations support our hypothesis that the inflammatory process underlying Crohn's disease affects bone homeostasis, leading to osteopenia. We will correlate bone density scores with data on biochemical markers of bone formation and bone resorption, disease activity, calcium intake and levels of cytokines at the end of the study to identify risk factors for osteopenia and osteoporosis. Our discoveries to date confirm the high frequency of osteopenia in patients with Crohn's disease. Our study will be the first large prospective longitudinal study measuring bone density and biochemical parameters of bone metabolism from time of diagnosis in children. This study is important because it avoids confounding variables encountered in cross-sectional studies. It also addresses the problem of bone loss in a particularly susceptible group of patients - children. The presence of osteopenia at a young age increases the lifetime risk of pathologic fractures and may affect linear growth. In addition, it is not clear whether Crohn's disease osteopenia improves with clinical remission. Therefore, it is of fundamental importance to understand the natural history and basic pathogenic mechanisms involved in Crohn's disease osteopenia. This knowledge will help to find specific therapies designed to treat osteopenia in Crohn's disease and perhaps other intestinal inflammatory conditions associated with bone loss.